Therefore, in this study, we selected 29 genes known to be involved in APP and Aβ processing: ADAM9, ADAM10, ADAM17, MEP1B, BACE1, BACE2, NCSTN, PSENEN, APH1B, LRRTM3, APLP1, APBA1, SORL1, TTR, GPR3, ECE1, ECE2, IDE, CST3, CTSB, CTSD, LYZ, MME, ACE, MMP3, A2M, PLAT, KLK6 and LRP1. We then analyzed the single, independent and the cumulative effect of protein coding variants in these genes from exome and genome sequencing data, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and UK. Here, APP is linked to Alzheimer disease.